E1 of α-ketoglutarate dehydrogenase defends Mycobacterium tuberculosis against glutamate anaplerosis and nitroxidative stress
Abstract
These studies shed light on the role of Mycobacterium tuberculosis (Mtb) 2-ketoglutarate (α-KG) dehydrogenase in fulfillment of noncanonical functions: defense against toxic aldehydes during glutamate anaplerosis and participation by two of its three enzymes in a previously undescribed antinitrosative defense. Analysis of the latter pathway revealed a peroxidase activity, which can be inferred to function as a peroxynitrite reductase as well. Heretofore, antioxidant enzyme systems were known to depend on electrons derived from the oxidant itself in dismutation reactions or derived directly or indirectly from NADPH or NADH. Here, electrons derived from the oxidative decarboxylation of central carbon metabolites α-KG and pyruvate to succinyl CoA (SucCoA) and acetyl CoA (AcCoA), respectively, serve as sources of reducing power.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- October 2015
- DOI:
- 10.1073/pnas.1510932112
- Bibcode:
- 2015PNAS..112E5834M